Aorta and Peripheral Arterial Disease in Hypertension

Aortic Dissection

The incidence of AoD is difficult to define given that dissections may be rapidly fatal and are frequently missed on initial presentation. When patients die before reaching, or shortly after presenting to, a hospital, death may be mistakenly attributed to another more common cause such as myocardial infarction (MI) or sudden cardiac death. A recent prospective population-based study reveals the incidence of AoD to be 6 cases per 100,000 person years, a significant increase from prior estimates. Risk of aortic dissection increases with age and male sex is a risk factor.

Classification of aortic dissections is based on two major systems, Stanford and DeBakey classification schema. The Stanford system is more widely used in clinical practice. Stanford type A dissections involve the ascending aorta with or without the aortic arch or descending aorta. Type B dissections involve the descending aorta without any involvement of the ascending aorta ( Fig. 45.2 ). Dissections involving the ascending aorta and aortic arch vessels are at highest risk for complications including stroke. These Type A dissections are best treated with emergent surgical management. A key factor in management of type B dissections is determining the presence of complications. Complications are defined as organ or limb malperfusion, progressive dissection, extra aortic blood collection (impending rupture), intractable pain, or uncontrolled hypertension. Short-term survival (3-year) appears to be unaffected by endovascular treatment in acute uncomplicated type B dissections compared with medical management as demonstrated by the INSTEAD trial. However, the INSTEAD XL-trial demonstrated that endovascular treatment in addition to optimal medical therapy is associated with improved 5-year aorta-specific survival and delayed disease progression.

On the other hand, complicated type B dissections may benefit from endovascular intervention as described in Study for the Treatment of complicated type B Aortic Dissection using Endoluminal repair (STABLE) trial, a prospective, multicenter study evaluating safety and effectiveness of a pathology-specific endovascular system (proximal stent graft and distal bare metal stent) for the treatment of complicated type B aortic dissection. It demonstrates that endovascular repair of complicated type B dissections with the use of a composite construct results in early clinical outcomes and aortic remodeling. Of note, patients treated acutely may be prone to aortic growth and may require close observation. Patient follow-up is still on-going.

Timely identification of the intimal disruption, location of dissection, and the involved vessels is crucial to prognosis as well as management decisions (open-surgical, medical, and/or endovascular). Classically, aortic dissection has been temporally categorized based on time of symptom onset with acute aortic dissection defined as diagnosis less than 14 days from symptom onset, and chronic defined as diagnosis greater than 14 days from symptom onset. Given the advances in care for patients with AoD, recent work proposes more nuanced categorization (hyperacute [symptom onset to 24 hours], acute [2 to 7 days], subacute [8 to 30 days], and chronic [>30 days]) based on Kaplan-Meier survival curves developed using the International Registry of Acute Aortic Dissection (IRAD: a consortium of research centers that are evaluating the current management and outcomes of acute aortic dissection involving 30 large referral centers in 11 countries), although this has not yet been formally adopted in guidelines.

Increased aortic wall stress and conditions that encourage aortic medial degeneration increase one’s risk of dissection. The majority of patients diagnosed with AoD have hypertension and the prevalence is increasing. Underlying genetic syndromes are not uncommon in patients with AoD, especially younger patients. Presentation of aortic dissection and complications are varied and numerous, with rapid assessment, diagnosis, and treatment resulting in much better outcomes.

Half of all patients with aortic dissections present with elevated systolic blood pressures (SBPs) (>150 mm Hg) and alternatively, 20% of patients present with hypotension and/or shock. As outlined in comprehensive thoracic aortic disease guidelines published in 2010, accurate blood pressure (BP) measurement at the time of dissection may be complicated in the setting of dissection-related occlusion of branching arteries, resulting in incorrectly low BP measurement in affected limbs. As such, BPs should be measured in both arms and, oftentimes, both legs to determine the highest central BP. Pulse pressure (PP), at the time of presentation, may also be a prognostic value in those with type A dissections. IRAD investigators recently determined that patients with type A AoD with narrow PP (<40 mm Hg) were more likely to have cardiac complications such as cardiac tamponade, whereas those with PP greater than 75 mm Hg were more likely to have abdominal aortic involvement.

Diagnosis imaging modalities to rule out aortic dissection are numerous. Meta-analyses demonstrate that contrast computed tomography (CT), transesophageal echocardiography (TEE), and magnetic resonance imaging (MRI) all provide valuable diagnostic information. Given that it is the most readily available imaging modality, CT is often the imaging modality of choice in hemodynamically stable patients. Those that are unstable are better suited for TEE.

Upon diagnosis of thoracic AoD, initial management should focus on decreasing aortic wall stress, by controlling heart rate and BP, to prevent propagation of the false lumen potentially leading to subsequent complications including rupture and/or malperfusion. Simultaneous discussion for definitive management should also be undertaken with surgical colleagues (regardless of dissection location, ascending or descending). Intravenous beta-blockade (in the absence of contraindications) should be administered to target a heart rate of less than 60 beats per minute. In patients with a contraindication to beta-blockade, nondihydropyridine calcium channel blockers should be administered with the goal of similar heart rate reduction (for example diltiazem or verapamil). Simultaneously, with heart rate control, the SBP should be addressed. If a patient’s SBP remains above 110 mm Hg with medication administration as noted above, angiotensin-converting enzyme inhibitors and/or other vasodilators should be given to further reduce SBP while maintaining adequate end-organ perfusion. Rapid diagnosis and initial blood pressure/heart rate management for acute type A dissection is the key for successful management transition to definitive surgical therapy. At our institution, we developed an aortic dissection flowsheet to facilitate and generalize the management ( Fig. 45.3 ). Appropriate initial heart rate control is critical before initiating vasodilator therapy, because the reflex tachycardia induced by vasodilators can increase aortic wall stress and worsen the existing dissection. Along similar lines, cautious beta-blocker administration in those patients with aortic insufficiency is warranted given the appropriate need for a compensatory tachycardia to maintain cardiac output.

The choice of beta-blocker is not crucial, as long as the desired heart rate and blood pressure lowering is achieved. However, intravenous labetalol may be the best initial choice given that it is both an alpha-receptor and beta-receptor antagonist. Theoretically, in addition to effective heart rate lowering, it also offers more BP lowering than beta-blockers that do not have additional alpha-blocking properties, potentially eliminating the need for multiple antihypertensive vasodilators. This is not an insignificant factor given that it is oftentimes difficult to reduce BP to endorsed levels and multiple antihypertensive agents may ultimately be needed. In addition to beta-blockers, other established agents for BP control during this critical time include intravenous nicardipine, nitroglycerin, fenoldopam among others whereas sodium nitroprusside should be considered a contraindication in the setting of acute type dissection as a result of an aggravating effect for spinal ischemia. An additional key intervention after diagnosis of aortic dissection is appropriate pain control. Sympathetic activation in setting of uncontrolled pain may worsen a patient’s tachycardia, raise BP, and will be difficult to treat.

Not surprisingly IRAD investigators demonstrated that uncomplicated type B dissections with appropriately controlled pain and hypertension have lower in-hospital mortality than those patients with uncontrolled hypertension and/or pain. Interestingly, the basis for the widely accepted need for intensive SBP control (less than 120 mm Hg) in acute aortic dissection is decades old case series evidence and although the recommendation is class I, it is level of evidence C. This suggests that further investigation of BP goals in acute medical treatment of aortic dissection is needed.

Following initial stabilization with intravenous antihypertensives, and in certain cases surgical management (open or endovascular) based on the location and complexity of the dissection, most patients will require long-term antihypertensive treatment. This should include a beta-blocker plus additional classes of BP lowering medications as detailed later.

Long-Term Blood Pressure Management Following Repair of Type A Dissections

In-hospital mortality for type A dissections has decreased from 31% to 22% in the past 17 years in the IRAD registry. Interestingly, more contemporary large single center data reflect a lower in-hospital mortality rate of closer to 10%. As such, long-term management strategies for these patients is crucial to prevent future events and complications. Data with respect to long-term survival of patients with repaired type A dissections are not robust, although the IRAD investigators report relatively high 3-year survival among patients who survived operative repair of their dissection. The study of patient characteristics impacting survival primarily focuses on preoperative and intraoperative characteristics, such as a patient’s comorbidities and the type of repair chosen. However, a recent retrospective review of patient characteristics impacting long-term outcomes following type A dissection repair, highlights the importance of blood pressure control and choice of antihypertensive medication, even after operative repair.

Amongst patients who survived operative repair, four main factors, male sex, Marfan syndrome, elevated SBP, and the absence of beta-blocker therapy significantly impacted the need for reoperation. Further, at 10-year follow-up, of those patients that maintained an SBP less than 120 mm Hg, only 8% required reoperation, compared with 26% in patients with SBP between 120 and 140 mm Hg, and 51% in those with SBP greater than 140 mm Hg. Similarly, patients taking beta-blockers at 10 years postrepair had an 86% freedom from reoperation, compared with 57% for those not taking beta-blockers. The IRAD investigators demonstrate similar beneficial effects of beta-blockade in survivors of type A AoDs, albeit over a shorter follow-up time (less than 5 years). Although the data are retrospective and include relatively low numbers, the pathophysiologic mechanism is sound. Beta-blockers, and strict BP control, diminish stress on the already diseased aorta, with a concurrent decrease in dP⁄dT (impulse), resulting in less aortic damage over time. Further long-term prospective study is needed, but it is very reasonable to aim for strict BP control in this subgroup of patients, with beta-blocker therapy as a first-line agent.

Long-Term Blood Pressure Management Type B Dissections

Recently, management paradigms of type B dissections have shifted based on the use of thoracic endovascular aortic repair (TEVAR) in complicated dissections, and some suggestion that even uncomplicated low-risk patients may demonstrate long-term benefit from preemptive or early endovascular repair. Irrespective of interventional management, control of BP remains a hallmark of immediate and long-term management of type B AoDs.

Similar to type A dissections, no high-level of evidence data exist regarding specific BP goals in patients with a history of type B AoD. Current guidelines recommend BP control similar to that of the general population ; however this may change in the wake of results from the SPRINT BP trial that demonstrated increased survival with more intensive BP goals in the general population. Beta-blockers are currently recommended in all patients with type B AoD based on data in Marfan syndrome patients that beta-blockade attenuates aneurysmal expansion. A recent systematic review attempted to establish the efficacy of beta-blockers versus other antihypertensives in this patient population. Unfortunately, no randomized control trials (RCTs) compare first-line beta-blockade with other first-line antihypertensive medications in the treatment of chronic type B AoD. The authors conclude that it is unknown whether beta-blockers as first-line therapy is appropriate, and future randomized controlled trials are needed.

However, there are some nonrandomized data to help guide clinical decision-making. A study of 71 patients with type B dissection that survived to hospital discharge, with approximately of 4 years of follow-up, suggests benefit of beta-blockade. Of the 50 patients treated with beta-blockers chronically, 10 required surgery for aortic dissection. This stands in contrast to 9 of 20 patients not treated with beta-blockers who required surgery for aortic dissection. Contrasting that data is a study from 2008, of patients with type B AoD treated medically with an average of 2.5 years of follow-up. Multivariate analysis did not demonstrate a reduction in long-term aortic events with beta-blocker administration, but did see a benefit in those patients prescribed angiotensin-converting enzyme inhibitors. Similarly, data from the 5-year IRAD follow-up do not demonstrate long-term benefit of beta-blockade on survival in patients with type B dissections. Interestingly, this multivariate analysis found that use of calcium channel blockers was associated with improved survival.

Aortic dissection is not a common end-point (primary or secondary) in large cardiovascular (CV) trials, including those looking at antihypertensive therapy. Taken as a whole, data with respect long-term BP management in type B dissections are limited at best and no specific class of antihypertensive demonstrates superiority aside from patients with Marfan syndrome.

Physical Activity and Lifestyle Recommendations Following Aortic Dissection

Lifestyle and physical activity restrictions are reasonable in patients with a history of thoracic aortic disease, even in those with repaired AoD, as a result of their effect on BP and aortic stress. Aerobic exercise should be encouraged in these patients because it is beneficial for overall cardiovascular health and wellbeing. However, sudden increases in dP/dt and blood pressure associated with certain physical stressors, particularly isometric exercise, may trigger AoD or rupture of aneurysms. Guidelines recommend advising patients to refrain from activities such as weightlifting and sports that may result in thoracic stress and trauma, or involve rotational movement while straining or breath-holding (Valsalva maneuver). Similarly, the sudden increase in aortic stress and systemic arterial pressure produced by activities such as lifting boxes and moving furniture should preclude patients with a history of TAD from the occupations.